Pages

Sunday, 20 January 2013

Endometriosis
is usually described as some variation of ‘patches of endometrium-like tissue
growing elsewhere in the body’. This description though throws up several
questions. For example, if endometriosis is related to the normal endometrium,
what can this tell us about the disease and what is the connection between the
two tissue types?

Initially
the similarity of endometriosis to the normal endometrium led academics to
believe endometriotic lesions were seeded in their locations by the backward
flow of endometrial cells during menstruation. This made sense at the time
because backward flowing menstruation (retrograde menstruation) is a thing that
happens and the fact that endometrial cells were entering the pelvic cavity and
endometriosis appeared to be endometrial in character seemed too much of a
coincidence.

However,
retrograde menstruation occurs almost universally in women of reproductive age,
yet endometriosis affects around 10% of women, so clearly there was still
something missing from this argument. Maybe the normal endometrium of women
destined to have endometriosis is somehow different from other women. These
days technology is such that we can analyse thousands of properties of cells at
the molecular level, allowing an unprecedented degree of detailed
characterisation of all the tissue types in the human body. Severalstudies
have focussed on characterising the endometrium of women with and without
endometriosis and found that; yes the endometrium in women with endometriosis
is indeed different. The endometrium from women with endometriosis appears to
have a higher ability to survive,
proliferate and invade,
seemingly filling in the missing part of the retrograde menstruation theory.

But, like
all great mystery stories, the case is never wrapped up in a neat little
package so early on. In recent years more and more evidence is coming to the
fore, challenging the theory of retrograde menstruation. In particular there is
now quite a significant amount of evidence to show the displaced endometrium
that defines endometriosis is, in fact, present before youwereevenborn. There are also
rare documented cases of endometriosis in men, women who cannot menstruate and
non-menstruating primates;
so clearly there is the need for some radical re-thinking.

Maybe we’ve
had the whole thing upside-down; maybe it is not the endometrium that dictates
the fate of endometriosis, but endometriosis that dictates the fate of the
endometrium. A collaborative research effort has provided some evidence to this
very end (you can read the full article here).
The authors of this study experimentally induced endometriosis in baboons by
injecting endometrial cells into the pelvic cavity and letting them form endometriotic
implants. They then compared the expression of genes within the endometrium of
the baboons with experimentally induced endometriosis and disease free baboons
over the course of 16 months. What they found was that the presence of
endometriosis (even in its very early stages) led to marked changes (a total of
4,331 genes were altered) in the normal endometrium.

This
potentially turns accepted wisdom on its head, in that women with endometriosis
are not born with a defective endometrium that gives rise to endometriosis via
retrograde menstruation. Rather, if we are to take all the above evidence into
account, it appears endometriosis is a condition you are born with that, when
the endometriotic implants ‘mature’ lead to changes in the function of the
normal endometrium, thus perhaps also accounting for the fertility issues women
with endo suffer from.

However, one
big questions still remains – how does endometriosis communicate with the
normal endometrium to illicit these changes?If we disregard the notion that endometrial cells can display quantum entanglement
then there must be a signalling pathway between the two cell types. The first
idea that comes to mind is something to do with the production of inflammatory
factors by endometriotic lesions. Lesions produce a number of inflammatory
factors that are also regulators of gene expression which, hypothetically,
could travel to the normal endometrium and alter its gene expression, but that’s
just an educated guess.

Even with
new evidence making us rethink the development of endometriosis, invariably we
find ourselves with more questions than answers - for example:

If the
endometriotic implants are removed, do the changes to the normal endometrium
revert back, or are the changes induced by endometriosis permanent?

If displaced
endometrium is found before birth, how does it get there? Müllerianosis?
Mesenchymal stem cells? Both? Something else?

What are the
genetic/epigenetic/environmental factors that influence the displacement of
endometrial cells?

Why does
endometriosis only occur in certain primates species?

Does
retrograde menstruation have any role to play in endometriosis and if not, why
not? Could some cases of endometriosis be due to retrograde menstruation and
others not, meaning there are multiple pathways to endometriosis development?

There is
still a long way to go before we completely comprehend endometriosis, but with
each passing year the walls blocking our understanding are chipped away until
eventually, the truth will be revealed.

Endometriosis Update

Endometriosis is an enigmatic disease, little is known about its origins, but it affects the lives of millions of women around the world. Despite the apparent lack of advancement in the field of endometriosis research, progress is slowly being made. The problem is that this progress is very rarely reported accurately to the public in a way everyone can understand. This Blog aims to report what is going on in the area of endometriosis research in plain and simple terms, so that everyone can keep up to date. Updates will be pretty sporadic but I'll try to report items of interest as often as possible.